Synthesis of Triquinane Natural Products

VIII Synthesis of Triquinane Natural Products O O O 1.N0BH4... 

The synthesis of other angularly fused triquinanes as well as linearly fused sesquiterpenes such as hirsutene and capnellene quickly followed. Many general methods for the synthesis of cyclopentanoid natural products emerged as a result of the target-oriented effort [6]. These accomplishments have been reviewed extensively on numerous occasions [7]. This chapter reviews the history of retigeranic acid from its isolation and structure determination to published approaches to its synthesis and the four total syntheses accomplished to date. 

Acetone- or acetophenone-sensitized irradiation of the enones yields the reeurranged ketones (213, 214) which are described as useful substrates for the synthesis of polyquinane natural products. The enones (215) can be converted by photosensitized irradiation into the diquinanediones (216). Irradiation of (215) in acetone gives a low yield of the tricyclic ketone (217). This ketone, while stable in the dark, is photochemically converted into the diquinanedione (215). The authors present evidence that this conversion results from fission of the cyclopropyl bond to yield the biradical (218). Demuth and Hinsken have reported the use of the oxardi-ir-methane rearrangement in the synthesis of annelated triquinanes. Thus the photo conversion of the enone (219) affords the tetracyclic ketone (220,72%). In an analogous reaction the enone (221) is converted into the isomeric ketone (222,70%). ... 

The following questions are based on a total synthesis of isocomene, an angular triquinane natural product. 

The arene-olefin meta-photocycloaddition approach to triquinane natural products is further illustrated this year with a three-step total synthesis of ( )-silphinene (5) starting from 2-bromotoluene (1). Thus, irradiation of the arene-olefin (2) derived from (1) gave a 1 1 mixture of the photoadducts (3) and (4) in 70% yield. Regioselective reductive cleavage of the cyclopropane bond in (3),... 

The intramolecular PKR was used by Fox and Pallerla (150) to obtain a key intermediate in the enantioselective synthesis of (—)-pentalenene 176, the unnatural enantiomer of the angular triquinane natural product. Using Co2(CO)8 (60) mol%) as catalyst in tolnene and 1 atm of CO, enantiomerically enriched (91% ee) cyclopropene 174 gave the PK addnct 175 (4 1 dr) in 64% isolated yield. The use of the known PKR promoter tetramethylthiourea (TMTU) was found to be critical in obtaining good yield of the desired tricyclic product (Scheme 80). 

Sequential pyrrolidine and hydantoin ring-forming reactions via intramolecular [2+3] cycloaddition have been applied to the stereoselective solid-phase synthesis of conformationally constrained tricyclic triazacyclopenta [C]pentalene scaffold 43 < 1999JOC8342>. These novel compounds 43 share the structural complexity characteristic of certain alkaloid natural products, angular triquinanes. The retrosynthetic analysis is shown in Scheme 87. 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

For example, ( )-hirsutene, a member of the triquinane class of natural products, has been prepared by tandem radical cyclization as shown in equation 132801. Also, in a key step in the synthesis of silphiperfolene, the tricyclic ketal precursor oxosilphiperfolene was generated by a tandem cyclization process (equation 133)805. The desired enantiomer was generated in a 5 2 excess over the unwanted one. 

Hua has used the products of Pauson-Khand cycloadditions for syntheses of optically active pental-enene and racemic pentalenolactone E methyl ester. The racemic ketone in the first case was converted to the necessary optically active intermediate by kinetic resolution via 1,4-addition of an optically active allyl sulfoxide anion. These represented the first synthesis of natural products containing the angularly fused triquinane skeleton from bicyclic Pauson-Khand products (equation 53 and Scheme 20). ... 

Since our direct route to angularly fused triquinanes from cycloaddition of l-(4-pentynyl)cyclopen-tenes is limited to trisubstituted alkenes and simple terminal alkynes, bisnorisocomene, but not iso-comene itself, could be prepared (Scheme 22). However, this limitation is not a factor for most other compounds in this class of natural products, and the steric interactions described earlier worked to our advantage in a diastereocontrolled synthesis of pentalenene (see structure. Scheme 20). The natural product was obtained by subjecting the product of Scheme 14 to the sequence i, Li, NH3, MeOH ii, MeLi, Et20 iii, p-TsOH, benzene, reflux. ... 

In principle, substrates could be designed to allow an application of the tandem sequence to the synthesis of a variety of natural products, particularly the angularly fused triquinanes 53-56 illustrated in Figure 2. 

---